Figure 4.

Activation of PKR and interaction with Ras activation and signaling towards p38. (A) In infected cells, recognition of a viral RNA results in PKR dimerization, autophosphorylation and activation. While activated PKR can directly phosphorylate eIF2α resulting in inhibition of protein synthesis, its indirect effect in the stress response by ATF activation could displace the equilibrium towards active unphosphorylated eIF2α to maintain protein synthesis. (B) Activation of the Ras oncogene that results in cell transformation can activate the p38 kinase by different routes. Activation of Ras also inhibits PKR activation by still unknown mechanism, this should result in limited PKR activation and consecutive p38 activation by this route, consecutive to viral infection. Dashed arrows indicate the presence of known or postulated intermediates.